Q&A

Donepezil minimally effective for patients with vascular dementia

J Fam Pract. 2004 March;53(3):172-188
By
Kenneth H. Johnson, DO
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  • BACKGROUND: Donepezil provides some benefits in cognition, global function, and activities of daily living for patients with mild to moderate dementia from Alzheimer disease. There has been no conclusive evidence of similar beneficial effects of cholinergic agents in vascular dementia.
  • POPULATION STUDIED: The researchers studied an international group of men and women (n=603), average age 74 years, with Mini-Mental State Examination (MMSE) scores between 10 and 26 (out of a possible 30) and radiographic abnormalities consistent with cerebrovascular disease. Patients were classified as having probable vascular dementia (70%) or possible (30%) vascular dementia according to criteria of the National Institute of Neurologic Disorders and Stroke.
  • STUDY DESIGN AND VALIDITY: This was a 24-week, double-blind, randomized (masked allocation) study. Patients received single daily doses of donepezil (5 or 10 mg) or matching placebo. Researchers performed psychometric evaluations, physical and neurological examinations, laboratory determinations, and measurements of vital signs at screening, baseline, and (together with checks for medication compliance and adverse events) at weeks 6, 12, 18, and 24.
  • OUTCOMES MEASURED: The primary efficacy outcome measured was cognition as assessed by the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician’s Interview-Based Impression of Change-Plus version (CIBIC-plus). Secondary efficacy endpoints were based on the MMSE, the Sum of the Boxes of the Clinical Dementia Rating (CDR-SB), and the Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS).
  • RESULTS: While the donepezil-treated groups showed statistically significant improvement as measured by the ADAS-cog (2 points improvement vs no change in placebo group), as many patients got worse as got better as measured by the CIBIC-plus. MMSEs improved by 1.04 ± 0.21 (P<.05) and 1.49 ± 20 (P<.001) points in the 5- and 10-mg groups, respectively, compared with 0.39 ± 0.23 in the placebo group. Activities of daily living did not deteriorate as much in the treatment groups—0.64 ± 0.36 (P<.05) for the 5-mg group and 0.53 ± 0.38 (P<.05) for the 10-mg group, compared with 1.44 ± 0.42 for placebo.
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PRACTICE RECOMMENDATIONS

Donepezil (Aricept—a potent acetylcholin-esterase inhibitor) had small effects on mentation for patients with mild to moderate vascular dementia as measured by validated instruments of cognition.

Donepezil’s side effects are similar to placebo at 5 mg but double at 10 mg, with no improvement in the patient’s cognition. Even though this medication was minimally effective, there are no other highly effective medical treatments for vascular dementia. Therefore, if a patient chooses a trial of donepezil, the lower, 5-mg dose should be offered.

The medication’s effect is likely a class effect and not an individual drug effect; therefore, rivastigmine (Exelon) and galantamine(Reminyl) are 2 other acetylcholinesterase inhibitors that should also be considered. Cost is similar for all 3 drugs at about $130.00 per month.

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